We have recently developed a general synthetic method whereby the CD ring system of the cardiac aglycones can be constructed. Our method involves acid-catalyzed cyclization o a suitable olefinic epoxide, and should be applicable to a wide variety of compounds. With this model work finished, we propose to begin the total synthesis of representative cardenolides and bufadienolides, compounds which are well known for their remarkable cardiotonic and cytotoxic properties. In addition to syntheses of digitoxigenin and scillarenin, we hope to show that our method is useful for the synthesis of C18 oxygenated aglycones such as holantogenin. We further propose a new method for the synthesis of the butenolide and alpha-pyrone lactone rings characteristic of these compounds, and propose to synthesize aglycone analogues containing an alpha-methylenebutyrolactone side chain.